| First Author | Windahl SH | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 6 | Pages | 2294-9 |
| PubMed ID | 23345419 | Mgi Jnum | J:193820 |
| Mgi Id | MGI:5469750 | Doi | 10.1073/pnas.1220811110 |
| Citation | Windahl SH, et al. (2013) Estrogen receptor-alpha in osteocytes is important for trabecular bone formation in male mice. Proc Natl Acad Sci U S A 110(6):2294-9 |
| abstractText | The bone-sparing effect of estrogen in both males and females is primarily mediated via estrogen receptor-alpha (ERalpha), encoded by the Esr1 gene. ERalpha in osteoclasts is crucial for the trabecular bone-sparing effect of estrogen in females, but it is dispensable for trabecular bone in male mice and for cortical bone in both genders. We hypothesized that ERalpha in osteocytes is important for trabecular bone in male mice and for cortical bone in both males and females. Dmp1-Cre mice were crossed with ERalpha(flox/flox) mice to generate mice lacking ERalpha protein expression specifically in osteocytes (Dmp1-ERalpha(-/-)). Male Dmp1-ERalpha(-/-) mice displayed a substantial reduction in trabecular bone volume (-20%, P < 0.01) compared with controls. Dynamic histomorphometry revealed reduced bone formation rate (-45%, P < 0.01) but the number of osteoclasts per bone surface was unaffected in the male Dmp1-ERalpha(-/-) mice. The male Dmp1-ERalpha(-/-) mice had reduced expression of several osteoblast/osteocyte markers in bone, including Runx2, Sp7, and Dmp1 (P < 0.05). Gonadal intact Dmp1-ERalpha(-/-) female mice had no significant reduction in trabecular bone volume but ovariectomized Dmp1-ERalpha(-/-) female mice displayed an attenuated trabecular bone response to supraphysiological E2 treatment. Dmp1-ERalpha(-/-) mice of both genders had unaffected cortical bone. In conclusion, ERalpha in osteocytes regulates trabecular bone formation and thereby trabecular bone volume in male mice but it is dispensable for the trabecular bone in female mice and the cortical bone in both genders. We propose that the physiological trabecular bone-sparing effect of estrogen is mediated via ERalpha in osteocytes in males, but via ERalpha in osteoclasts in females. |
